Incorporation of all-trans-retinoic acid (ATRA) into the treatment of acute promyelocytic leukemia (APL), a type of acute myeloid leukemia (AML), revolutionized the therapy of cancer in the last decade and introduced the concept of differentiation therapy. ATRA, a physiological metabolite of vitamin A (retinol), induces complete clinical remissions (CRs) in about 90% of patients with APL. In contrast to the cytotoxic chemotherapeutics, ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes in patients with APL. However, remissions induced by ATRA alone are transient and the patients commonly become resistant to the therapy, leading to relapses in most patients and thus limiting the use of ATRA as a single agent. Therefore, ATRA is currently combined with anthracycline-based chemotherapy, and this regimen dramatically improves patient survival compared to chemotherapy alone, curing about 70% of the patients. However, 30% of APL patients still relapse and die in five years. Recently, arsenic trioxide (As2O3) was proven to be highly effective in inducing CRs not only in APL patients relapsed after ATRA treatment and conventional chemotherapy but also in primary APL patients. Despite the well-documented clinical efficacy of ATRA, molecular mechanisms responsible for development of ATRA resistance are not well understood. Based on in vitro and clinical observations, several mechanisms, including induction of accelerated metabolism of ATRA, decreased bioavailability and plasma drug levels, point mutations in the ATRA-binding domain of promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARα) and other molecular events have been proposed to explain ATRA resistance. In this review, the molecular mechanisms of ATRA-induced myeloid cell differentiation and resistance are discussed, together with novel clinical approaches to overcome ATRA resistance in APL.

OBJECTIVE: Premarital hemoglobinopathy screening is one of the important procedures of hemoglobinopathy control program. This is the first report about the prevalence of hemoglobinopathies in Kocaeli. METHODS: Study covered screening from July 2005 to the end of the December 2008. Under the auspices of the Ministry of Health and Regional Health authorities blood samples of the couples were obtained during admission to the wedding office. Complete blood counts and hemoglobin variant analysis were performed with automatic counter and high pressure liquid chromotography technique. A genetic counseling was given to carriers of abnormal hemoglobins. RESULTS: A total of 88888 people were screened. The frequency of β -thalassemia trait and sickle cell anemia trait were 0.89% and 0.05% respectively. The frequency of high risk couples was 0.01%. CONCLUSION: The prevalence of β -thalassemia trait and sickle cell anemia trait was quite low as a reflection of the frequency of eastern and northern Anatolia and migration to Kocaeli from these geographic regions. Although frequency is low, chronic transfusion requirement, high cost of chelating, organ damage, painful crisis and other crisis, availability of stem cell transplantation for a limited number of patients with compatible sibling donors justify premarital screening studies even in less prevalent regions as Kocaeli.

OBJECTIVE: There is no diagnostic tool to identify which bacterial catheter colonization may eventually result in bloodstream infection. We speculated that a faster growth or repeated positivity of serial blood cultures drawn from the catheter might herald catheter-related bacteremia (CRB) before the onset of fever. METHODS: We designed a prospective observational pilot study. All patients who underwent hematopoietic stem cell transplantation (HSCT) were prospectively included in the study over 10 months. Daily catheter-drawn blood cultures (DBC) were performed. We recorded the growth time of each blood culture and bacterial isolation. A fast-growing blood culture (positive <12 hours) or at least 2 positive identical cultures within 4 consecutive days in the DBC were defined as a marker of risk for CRB. The value of this marker to predict CRB was investigated.RESULTS: A total of 82 patients (843 days of catheter) were included in the study. Fast- growing or repeated identical cultures were present in 20 patients; among them, 15 had clinical criteria of CRB. Among 62 patients without fast-growing or repeated identical cultures, 11 met the criteria of CRB. Consequently, for the defined marker of risk, the positive predictive value was 75%, negative predictive value 82%, sensitivity 70%, and specificity 91%. Sixty-two blood cultures were needed to detect one case of CRB prior to the onset of fever. CONCLUSION: The use of routinely drawn catheter-blood cultures does not seem to be a useful tool for predicting CRB in HSCT patients.

OBJECTIVE: In anemic patients, the correlation between serum erythropoietin (sEpo) level and the severity of anemia has been reported previously. However, in different anemia groups, different sEpo levels are measured in patients with similar hemoglobin levels and the etiology of this situation could not be explained. METHODS: We evaluated hemoglobin and sEpo levels in 31 iron deficiency anemia, 26 Fanconi anemia (FA), 21 thallasemia intermedia (TI), 15 acute lymphoblastic leukemia (ALL) patients at presentation and 12 healthy controls. RESULTS: In all disease groups, an inverse linear correlation was shown between hemoglobin and logarhytmic sEpo level. The covariance analyses according to corrected hemoglobin levels exhibited the highest sEpo level in FA, followed by ALL, TI and iron deficiency anemia, sequentialy. CONCLUSION: There was no statisticaly significant difference of sEpo levels in FA patients in terms of androgen treatment and this finding supports that androgen affects erythropoisis directly, and has no effect on erythropoietin. The results indicate that there is no erythropoietin deficiency in the anemia of these patients and the admnistration of exogenous erythropoietin offers no clinical benefit.

OBJECTIVE: We determined the morphological changes of erythrocytes in blood samples of diabetic patients with varying levels of hyperglycemia with normo- and hyper-cholesterol concentrations and compared them with cells of healthy subjects.METHODS: The shape analysis was carried out by shape descriptors based on projected area, perimeter and form factor, as measured by the processing of erythrocyte images. Blood smears were collected from normal subjects and from glycemic subjects with normo- and hyper-cholesterol levels. After image processing techniques like edge enhancement, thresholding, filtering, contour extraction, and pattern analysis and recognition, the images were used for shape analysis. RESULTS: The shape parameters, which quantified the changes in erythrocytes in diabetic subjects with normal cholesterol level, showed significant deviation from the shape of normal cells. Cells of diabetic subjects with hyper-cholesterol level showed more deviation than cells with normal cholesterol.CONCLUSION: These changes lead to hyper aggregation and to a decrease in deformability of erythrocytes and hence increase microcirculatory complications.

OBJECTIVE: Variceal bleeding in cirrhosis is mainly due to platelet activation defect and secondary to coagulation defects. Secretion is an important process which release procoagulants for hemostasis. In the present investigation we have evaluated the secretory function of platelets in liver cirrhosis and also the simultaneous changes in cytosolic calcium (Ca2+) and the polymerization of actin in agonist- stimulated platelets in vitro.

METHODS: Liver cirrhotic patients with (n=27) or without (n=23) bleeding complication were included in the study. Control subjects (n=50) were also utilized for the study to compare the analytical data. Platelets were activated by collagen in vitro and the secretory response was assessed by the levels of nucleotides, serotonin, pyrophosphate (PPi) and inorganic phosphate (Pi) secreted into the extracellular fluid of the platelet suspension at various time intervals. During the course of secretion the alteration in the polymerization of actin was monitored simultaneously with the changes in the cytosolic Ca2+ level.

RESULTS: The secretory response of platelets to collagen was significantly low in both bleeders and non-bleeders when compared to that of normal subjects. During secretion, low level of actin polymerization and cytosolic Ca2+ level were observed in the platelets of bleeders than in non-bleeders and normal subjects. The low secretory capacity of cirrhosis platelets could be correlated with low levels of actin polymerization and cytosolic Ca2+. The alterations were highly significant in the platelets of bleeders when compared to those of non-bleeders.

CONCLUSION: The defective secretory activity of platelets in cirrhosis bleeders might be partly due to low polymerization of G-actin to F-actin which is required for platelet shape change and for the release of procoagulants. Cytosolic Ca2+ level seems to influence actin polymerization and thereby impairs platelet secretory response to agonists in cirrhosis patients with bleeding complication.

Myeloid sarcoma of urinary bladder is a rare disorder. We report a 71-year old man with hematuria. He was also under follow up for unclassified myeloproliferative/ myelodysplastic disorder, diagnosed 2 months ago. Abdominal ultrasonography and computed tomography findings were normal. Diagnostic cystoscopy revealed patchy areas of mucosal swelling with hyperemia. Histopathological examination of biopsies demonstrated a neoplasm composed of blasts showing myeloperoxidease positivity by immunohistochemistry. To our knowledge, current case is the first case of myeloid sarcoma without evidence of a mass lesion in the urinary bladder with a concurrent diagnosis of myelodysplastic /myeloproliferative disease, unclassifiable.

Extensive fibrosis in myelodysplastic syndromes (MDS) is distinctly infrequent. Herein, we report three rare cases of hyperfibrotic MDS. This entity should be classified separately in the chronic myeloproliferative disease (CMPD)-MDS group due to variable clinical presentation and poor prognosis.

Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.